| 1. |
- Aho, Sonja, et al.
(författare)
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Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study)
- 2024
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary The location of the primary tumor in the right colon, left colon, or rectum affects the efficacy of biological drugs used in the treatment of metastatic colorectal cancer, but how? We examined how the primary tumor location affects disease characteristics, treatability, quality of life, and outcome in a real-life study population of 1080 Finnish patients in the RAXO study. The primary tumor location correlates with the location of metastases, the frequency of gene mutations, how often metastases can be operated upon, long-term survival after curative surgery or palliative chemotherapy, and the quality of life during the disease trajectory. The primary tumor location is a helpful surrogate for clinicians working with metastatic colorectal cancer patients in estimating the clinical course of the disease. This study cannot identify the reasons for the associations, i.e., whether it is the primary location per se, the different mutations, or other reasons.Abstract The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right vs. left sided). We studied right colon vs. left colon vs. rectal PTL in a real-life study population (n = 1080). Health-related quality of life (HRQoL) was assessed multi-cross-sectionally with QLQ-C30, QLQ-CR29, EQ-5D, and 15D. A chi-square, Kaplan-Meier, and Cox regression were used to compare the groups. The PTL was in the right colon in 310 patients (29%), the left colon in 396 patients (37%), and the rectum in 375 patients (35%). The PTL was associated with distinct differences in metastatic sites during the disease trajectory. The resectability, conversion, and resection rates were lowest in the right colon, followed by the rectum, and were highest in the left colon. Overall survival was shortest for right colon compared with left colon or rectal PTL (median 21 vs. 35 vs. 36 months), with the same trends after metastasectomy or systemic therapy only. PTL also remained statistically significant in a multivariable model. The distribution of symptoms varied according to PTL, especially between the right colon (with general symptoms of metastases) and rectal PTL (with sexual- and bowel-related symptoms). mCRC, according to PTL, behaves differently regarding metastatic sites, resectability of the metastases, outcomes of treatment, and HRQoL.
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| 2. |
- Betzholtz, Per-Eric, et al.
(författare)
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What do population viability analyses tell about the future for Baltic Dunlin Calidris alpina schinzii and Montagu’s Harrier Circus pygargus on Öland?
- 2010
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Ingår i: Ornis Svecica. - Lund : Swedish Ornithological Society. - 1102-6812 .- 2003-2633. ; 20, s. 93-102
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Tidskriftsartikel (refereegranskat)abstract
- Population viability analysis (PVA) has become an important tool in conservation biology. Even though detailed outcomes of PVA:s are constrained by data quality, it is a useful approach when the objective is exploratory, aiming to identify important parameters for viability or to guide future field work on endangered species. In this study we perform PVA:s based on scarce data to explore viability of two endangered bird species, Baltic Dunlin and Montagu’s Harrier, on Öland. Our simulation results underline that both species are under severe threats, with a median time to extinction of 24 years in Baltic Dunlin and 63 years in Montagu’s Harrier. Sensitivity analyses show that population growth rate is the most important factor for the model outcome in both species. Since there are no apparent threats for adult birds on Öland, this suggests that conservation measures should focus on improving conditions for successful breeding on the island. In additional simulations we explore some threats in more detail. In the case of Baltic Dunlin nest predation of eggs and chicks increase the extinction risk. In Montagu’s Harrier viability increases if breeding attempts within agricultural areas are detected and safeguarded. In order to enhance the PVA model, and build a stage-structured model, we suggest that detailed data on fecundity and survival should be collected.
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| 3. |
- Bonnedahl, Jonas, et al.
(författare)
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Characterization, and comparison, of human clinical and black-headed gull (Larus ridibundus) extended-spectrum β-lactamase-producing bacterial isolates from Kalmar, on the southeast coast of Sweden
- 2010
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 65:9, s. 1939-1944
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance is one of the great challenges for modern healthcare. In Gram-negative bacteria, CTX-M-type extended-spectrum beta-lactamases (ESBLs) have been rapidly spreading through Europe since the early 2000s. In Sweden, ESBL-producing Escherichia coli are still rare, but a 3-fold increase has been seen from 2004 to 2007. Enterobacteria and normal flora of wild animals, with or without antibiotic resistance traits, constitute a potential source of human infection and colonization. We studied wild birds with the aim to understand the environmental dissemination of antibiotic resistance and, focusing on clinically relevant resistance types, we made comparisons with human clinical samples. In this study, ESBL-producing human clinical isolates and isolates from juvenile black-headed gulls from Kalmar County hospital and the city of Kalmar, respectively, on the southeast coast of Sweden, were characterized and compared. Despite a low frequency of antibiotic resistance among the isolates from gulls, ESBL-producing E. coli isolates were found, two with bla(CTX-M-14) and one with bla(CTX-M-15). The same CTX-M types were dominant among human ESBL isolates. In addition, gull isolates were dispersed among the human samples in the PhenePlate (TM) clustering system, indicating that they neither differ from the human isolates nor form any separate clonal clustering. The finding of CTX-M-type ESBLs in E. coli isolated from black-headed gulls in Sweden, where 'background resistance' is low, is consistent with an ongoing environmental spread of these plasmid-borne resistance genes. The results indicate that a potential for transfer between the human population and environment exists even in countries with a low level of antibiotic resistance.
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| 4. |
- Stedt, H, et al.
(författare)
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Tomato thymidine kinase-based suicide gene therapy for malignant glioma-an alternative for Herpes Simplex virus-1 thymidine kinase.
- 2015
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Ingår i: Cancer Gene Therapy. - : Springer Science and Business Media LLC. - 1476-5500 .- 0929-1903. ; 22:3, s. 130-137
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Tidskriftsartikel (refereegranskat)abstract
- Malignant gliomas (MGs) are the most common malignant primary brain tumors with a short life estimate accompanied by a marked reduction in the quality of life. Herpes Simplex virus-1 thymidine kinase ganciclovir (HSV-TK/GCV) system is the best characterized enzyme prodrug therapy in use. However, lipophobicity of GCV and low enzymatic activity of HSV-TK reduce the treatment efficacy. Tomato TK (ToTK) has shown high activity in combination with its specific substrate azidothymidine (AZT). The aim of this study was to evaluate whether ToTK/AZT could be used as an alternative to HSV-TK/GCV therapy. Both treatments demonstrated cytotoxicity in human MG cells in vitro. In vivo, both treatments decreased tumor growth and tumors were smaller in comparison with controls in mouse orthotopic MG model. Survival of ToTK/AZT-treated mice was significantly increased compared with control mice (*P<0.05) but not as compared with HSV-TK/GCV-treated mice. No significant differences were observed in clinical chemistry safety analyses. We conclude that both treatments showed a beneficial treatment response in comparison to controls on tumor growth and ToTK/AZT also on survival. There were no significant differences between these treatments. Therefore ToTK/AZT could be considered as an alternative treatment option for MG because of its favorable therapeutic characteristics.Cancer Gene Therapy advance online publication, 23 January 2015; doi:10.1038/cgt.2014.76.
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| 5. |
- Stedt, Johan, et al.
(författare)
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Antibiotic resistance patterns in Escherichia coli from gulls in nine European countries
- 2014
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Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The prevalence of antibiotic resistant faecal indicator bacteria from humans and food production animals has increased over the last decades. In Europe, resistance levels in Escherichia coli from these sources show a south-to-north gradient, with more widespread resistance in the Mediterranean region compared to northern Europe. Recent studies show that resistance levels can be high also in wildlife, but it is unknown to what extent resistance levels in nature conform to the patterns observed in human-associated bacteria.METHODS: To test this, we collected 3,158 faecal samples from breeding gulls (Larus sp.) from nine European countries and tested 2,210 randomly isolated E. coli for resistance against 10 antibiotics commonly used in human and veterinary medicine.RESULTS: Overall, 31.5% of the gull E. coli isolates were resistant to ≥1 antibiotic, but with considerable variation between countries: highest levels of isolates resistant to ≥1 antibiotic were observed in Spain (61.2%) and lowest levels in Denmark (8.3%). For each tested antibiotic, the Iberian countries were either the countries with the highest levels or in the upper range in between-country comparisons, while northern countries generally had a lower proportion of resistant E. coli isolates, thereby resembling the gradient of resistance seen in human and food animal sources.CONCLUSION: We propose that gulls may serve as a sentinel of environmental levels of antibiotic resistant E. coli to complement studies of human-associated microbiota.
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| 6. |
- Stedt, Johan, et al.
(författare)
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Carriage of CTX-M type extended spectrum beta-lactamases (ESBLs) in gulls across Europe
- 2015
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- Background: Extended spectrum beta-lactamases (ESBLs), a group of enzymes conferring resistance to third generation cephalosporins have rapidly increased in Enterobacteriacae and pose a major challenge to human health care. Resistant isolates are common in domestic animals and clinical settings, but prevalence and genotype distribution varies on a geographical scale. Although ESBL genes are frequently detected in bacteria isolated from wildlife samples, ESBL dissemination of resistant bacteria to the environment is largely unknown. To address this, we used three closely related gull species as a model system and collected more than 3000 faecal samples during breeding times in nine European countries. Samples were screened for ESBL-producing bacteria, which were characterized to the level of ESBL genotype groups (SHV, TEM), or specific genotypes (CTX-M). Results: ESBL-producing bacteria were frequently detected in gulls (906 of 3158 samples, 28.7 %), with significant variation in prevalence rates between countries. Highest levels were found in Spain (74.8 %), The Netherlands (37.8 %) and England (27.1 %). Denmark and Poland represented the other extreme with no, or very few positive samples. Genotyping of CTX-M isolates identified 13 different variants, with bla(CTX-M-1) and bla(CTX-M-14) as the most frequently detected. In samples from England, Spain and Portugal, blaCTX-M-14 dominated, while in the rest of the sampled countries blaCTX-M-1 (except Sweden where bla(CTX-M-15) was dominant) was the most frequently detected genotype, a pattern similar to what is known from studies of human materials. Conclusions: CTX-M type ESBLs are common in the faecal microbiota from gulls across Europe. The gull ESBL genotype distribution was in large similar to published datasets from human and food-production animals in Europe. The data suggests that the environmental dissemination of ESBL is high from anthropogenic sources, and widespread occurrence of resistant bacteria in common migratory bird species utilizing urban and agricultural areas suggests that antibiotic resistance genes may also be spread through birds.
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| 7. |
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| 8. |
- Uutela, Aki, et al.
(författare)
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Resectability, conversion, metastasectomy and outcome according to RAS and BRAF status for metastatic colorectal cancer in the prospective RAXO study
- 2022
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Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 127:4, s. 686-694
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Tidskriftsartikel (refereegranskat)abstract
- Background Outcomes after metastasectomy for metastatic colorectal cancer (mCRC) vary with RAS and BRAF mutational status, but their effects on resectability and conversion rates have not been extensively studied. Methods This substudy of the prospective RAXO trial included 906 patients recruited between 2011 and 2018. We evaluated repeated centralised resectability assessment, conversion/resection rates and overall survival (OS), according to RAS and BRAF status. Results Patients included 289 with RAS and BRAF wild-type (RAS and BRAFwt), 529 with RAS mutated (RASmt) and 88 with BRAF mutated (BRAFmt) mCRC. Metastatic prevalence varied between the RAS and BRAFwt/RASmt/BRAFmt groups, for liver (78%/74%/61%), lung (24%/35%/28%) and peritoneal (15%/15%/32%) metastases, respectively. Upfront resectability (32%/29%/15%), conversion (16%/13%/7%) and resection/local ablative therapy (LAT) rates (45%/37%/17%) varied for RASa and BRAFwt/RASmt/BRAFmt, respectively. Median OS for patients treated with resection/LAT (n = 342) was 83/69/30 months, with 5-year OS-rates of 67%/60%/24%, while systemic therapy-only patients (n = 564) had OS of 29/21/15 months with 5-year OS-rates of 11%/6%/2% in RAS and BRAFwt/RASmt/BRAFmt, respectively. Resection/LAT was associated with improved OS in all subgroups. Conclusions There were significant differences in resectability, conversion and resection/LAT rates according to RAS and BRAF status. OS was also significantly longer for RAS and BRAFwt versus either mutant. Patients only receiving systemic therapy had poorer long-term survival, with variation according to molecular status.
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| 9. |
- Werner, M, et al.
(författare)
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Autoimmune hepatitis in Sweden.
- 2007
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Ingår i: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. - 0036-5521. ; 42, s. 15-15
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Wåhlin, Anna, et al.
(författare)
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Swirls and scoops: Ice base melt revealed by multibeam imagery of an Antarctic ice shelf
- 2024
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Ingår i: Science Advances. - : NA. - 2375-2548. ; 10:31, s. 9188-
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge gaps about how the ocean melts Antarctica's ice shelves, borne from a lack of observations, lead to large uncertainties in sea level predictions. Using high-resolution maps of the underside of Dotson Ice Shelf, West Antarctica, we reveal the imprint that ice shelf basal melting leaves on the ice. Convection and intermittent warm water intrusions form widespread terraced features through slow melting in quiescent areas, while shear-driven turbulence rapidly melts smooth, eroded topographies in outflow areas, as well as enigmatic teardrop-shaped indentations that result from boundary-layer flow rotation. Full-thickness ice fractures, with bases modified by basal melting and convective processes, are observed throughout the area. This new wealth of processes, all active under a single ice shelf, must be considered to accurately predict future Antarctic ice shelf melt.
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